Third Rock Ventures Launches Tango Therapeutics with $55 Million
Series A Investment

Company targeting context-dependent vulnerabilities in cancers for
patients without effective treatment options

March 30, 2017 07:00 AM Eastern Daylight Time

CAMBRIDGE, Mass.--(EON: Enhanced Online News)--Third Rock Ventures, LLC today announced the launch of Tango
Therapeutics, a new cancer therapeutics company discovering and
developing novel medicines designed to target cancer vulnerabilities
beyond mutated oncogenes to deliver transformational new therapies for
patients.

Tango was launched with a $55 million Series A investment from Third
Rock Ventures. The company has established a robust product engine that
leverages advances in DNA sequencing and CRISPR-based target discovery
to generate breakthrough medicines that will provide deeper, more
sustained benefit than today’s targeted therapies, and extend the
benefit of available immuno-oncology agents.

“Cancers are complex genetic diseases marked by multiple lesions in each
tumor. These include genes that are turned on to drive cancer growth and
those that are inactivated and thus, unable to function as tumor
suppressors,” said Barbara Weber, M.D., Tango’s interim Chief Executive
Officer and a Venture Partner at Third Rock Ventures. “Loss of tumor
suppressor genes is a hallmark of cancer, but the genes, themselves, are
not tractable targets for drug discovery. The availability of
comprehensive DNA sequencing, coupled with CRISPR-enabled target
discovery, provides us with new paths to identify novel drug targets and
combinations that take advantage of vulnerabilities created by loss of
tumor suppressor gene function -- something we have been unable to do
effectively in the past. With the sophisticated genomics tools now
available, the time is right for Tango to take on this challenge and
focus on patients without effective treatment options.”

Tango is focused on three areas of drug development, each in
well-defined patient populations currently lacking effective treatment
options, and each with hallmarks of cancer that have not been targeted
yet. These include:

Loss of tumor suppressor gene function: A universal feature of
cancer is the inactivation of genes which normally protect against
tumor development. Tango is working to turn tumor suppressor gene loss
from cancer’s strength into a weakness by identifying associated
targetable vulnerabilities, an effect known as synthetic lethality.
Drugs against synthetic lethal targets have the potential added
benefit of effectiveness against cancer cells without damaging normal
cells.

Multiple oncogenic drivers: To address the multiple genetic
changes that give rise to cancer, Tango is working to identify novel
targets for rational combinations that will offer more robust
treatment effects than is possible with single-agent approaches.
Decades of cancer research have shown that with the right drug
combinations in the right patients, cancers can be curable.

Immune evasion: Complementing current, immune-cell-directed
cancer therapies, Tango is working to identify and target the genetic
alterations in cancer cells responsible for helping them avoid immune
destruction. Drugs against these targets could substantially increase
the benefit of current immuno-oncology drugs without increasing immune
damage to normal tissues.

What fuels each of Tango’s programs is an increasingly sophisticated
ability to utilize synthetic lethality, the interaction between two
genes that causes cell death when both are inactivated. In cancer cells,
one of these genes is inactivated by mutation; the other will be
inactivated by a drug. This approach leaves normal cells largely
unaffected, with the potential to greatly enhance anti-tumor efficacy
and reduce associated toxicity.

The first FDA-approved example of synthetic lethality in cancer
treatment is the use of PARP inhibitors for BRCA-mutant ovarian cancer.
Alan Ashworth, Ph.D., a scientific Founder of Tango, discovered that
combining a BRCA1/2 mutation and PARP inhibition creates synthetic
lethality. Recent data show that continuing treatment with a PARP
inhibitor after chemotherapy in patients with BRCA-mutant ovarian cancer
extends progression-free survival for more than two years, compared to
placebo. The Tango product engine is designed to systematically discover
other such context-specific vulnerabilities, uncovering weaknesses
created by genetic alterations in cancer and targeting them for
therapeutic benefit.

In executing this strategy, Tango will upend the traditional paradigm by
doing target discovery in cancer subgroups with a pre-defined patient
selection approach. The company will use data from DNA sequencing of
patient-derived tumor samples to define genetic contexts, and deploy
CRISPR-based target discovery techniques in those cancer subtypes to
identify novel drug targets.

Tango’s success will be driven by its depth of understanding of the
genetic subtypes of cancer, and corresponding insights into novel drug
targets and combinations uniquely relevant to each subtype. By shaping
discovery efforts in this way, Tango has the potential to reach the
clinic quickly, and with a clear plan for identifying the patients most
likely to benefit from each new treatment, an approach that will
increase both speed and probability of success in translating novel
target discoveries into transformational new medicines for patients.

The Tango founders are a group of internationally recognized scientists
and clinicians who have shaped the current state of knowledge and
practice in cancer biology and genetics, translational medicine and
CRISPR technology:

Alan Ashworth,Ph.D., FRS, President of the University of
California San Francisco Helen Diller Family Comprehensive Cancer
Center

Antoni Ribas, M.D., Ph.D., Professor of Medicine, Surgery, and
Molecular and Medical Pharmacology at the University of California Los
Angeles

About Tango Therapeutics

Tango Therapeutics is a biotechnology company developing novel medicines
for patients by discovering and drugging context-dependent
vulnerabilities in cancers. Tango was launched in 2017 by Third Rock
Ventures and is headquartered in Cambridge, Mass. For more information,
please visit www.tangotx.com.

About Third Rock Ventures

Third Rock Ventures is a leading healthcare venture firm focused on
disruptive areas of science and medicine to discover, launch and build
companies that make a dramatic difference in people’s lives. By
combining our team’s scientific vision, strategic leadership,
operational expertise and innovative deal-making capabilities, we
nurture bold ideas that translate into successful business enterprises.
Recognizing that the best way to create value for our investors is to
create value for patients, our companies are built on a solid foundation
of science, medicine, people and business strategy. For more
information, please visit www.thirdrockventures.com.